Background: There are major gaps in our knowledge regarding the short- and long-term effects of intermittent hypoxia, especially when it comes to linking genomic and cellular responses with the physiological adaptation. It is also not clear whether Chronic Sustained Hypoxia (CH) and Chronic Intermittent Hypoxia(CIH) have any impact in hyperglycemia. Objectives: To find out the effect of Chronic Sustained Hypoxia or Chronic Intermittent Hypoxia in diabetic rats on cellular transcriptional and Gene expression pathways (HIF 1α , i-NOS, e-NOS, Nitrite/Nitrate (NOx) & VEGF) with or without supplementation of Vitamin C. Methods: Rats were divided into twelve groups in two parts: Part I consists of Control, Vitamin C treated, Chronic Sustained Hypoxia exposure, Chronic Sustained Hypoxia + Vitamin C, Chronic Intermittent Hypoxia exposure, Chronic Intermittent Hypoxia + Vitamin C. Part II consists of Diabetes, Diabetes + Vitamin C, Chronic Sustained Hypoxia + Diabetes, Chronic Sustained Hypoxia + Diabetes + Vitamin C, Chronic Intermittent Hypoxia + Diabetes and Chronic Intermittent Hypoxia + Diabetes +Vitamin C. Rats were made diabetic by injecting alloxan monohydrate, 150 mg/kg b.wt; i.p. single dose. Rats were exposed to hypoxia for 20 days. The hypoxic environment was established in the hypoxic chamber (10 % O2 and 90% N2 )with the inflow of a mixture of room air and nitrogen that was regulated by an oxygen analyzer(model 175518A, Gold Edition, Vacuum Med). CO2 was absorbed by soda lime 27 granules, and excess humidity was removed by desicator. Temperature was maintained at 24-26°C. The chamber was opened twice a week for 1 h to clean the cages and replenish food and water. Serum HIF-1α, serum i-NOS, serum e-NOS and serum VEGF concentration were evaluated by ELISA technique and serum nitrate/nitrite concentration were estimated by using UV-Visible spectrophotometer. Results: Chronic Sustained Hypoxia, Chronic Intermittent Hypoxia increases and DM decreases serum HIF 1 conc. as compared to control. Chronic Sustained Hypoxia and Chronic Intermittent Hypoxia increases serum i-NOS, e-NOS and NOx conc.as compared to control. Diabetes M. causes increase in i-NOS and NOx but decreases e-NOS activities. DM with CH and DM with CIH shows significant elevation of serum i-NOS and reduction of serum e-NOS level as compared to only CH & CIH respectively. Vitamin C is found to be beneficial to reduce serum i-NOS and NOx conc.(but not in e-NOS) in all the experimental groups Serum VEGF concentration increases in all the experimental groups but incase of CIH, the rise of VEGF is lesser as compared to VEGF concentration in CH group. VEGF concentration is lesser in DM which is remarkably improved after Vitamin C supplementation. Conclusion: CH or CIH definitely alters HIF-1 α transcriptional pathways as well as NOS activities and changes VEGF gene expression by modulating its concentration in serum and provide hypoxia induce adaptability in physiological system. DM just oppose this adaptive mechanism which become worst incase of simultaneous exposure with CH or CIH. But interestingly supplementation of Vitamin C is found to be beneficial to combat both CH and CIH. It is also found to be an effective non enzymatic antioxidant to fight against alteration of hypoxia adaptive pathways in diabetic condition.