Although mercury is recognized as a hazardous chemical, its commercial importance and applications has led to an increase in occupational and environmental exposures in many parts of the world. This study evaluated the impact of HgCl2 on glucose homeostasis and the possible involvement of oxidative stress. In addition, the potential protective effects of the antioxidant Alpha Lipoic Acid (ALA) were investigated. Thirty Sprague Dawley rats were divided into five equal groups of six animals: Group 1 (control) received 0.5 ml distilled water; Group 2 (ALA) received 100 μg/kg of ALA; Group 3 (LDM) and Group 4 (HDM) received 250 and 500 μg/kg body weight of HgCl2, respectively; and Group 5 (HDM-ALA) received 500 μg/kg of HgCl2 and 100 μg/kg of ALA. Both HgCl2 and ALA were administered orally for 14 days. 1-2 drops of blood were collected six times with a minimum of 30 mins interval on glucose strips from the rat tail vein to determine fasting blood glucose and oral glucose tolerance test (OGTT). 3hrs post OGTT; the rats’ were anaesthetized with ketamine (90mg/kg b.w) and Xylazine (10mg/kg b.w) as a single intraperitoneal injection and the rats’ livers were removed for determination of the activities of reduced glutathione GSH), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation, indexed as Malondialdehyde (MDA) levels. Values are means ± SEM, compared by one way ANOVA. The fasting blood glucose (mmol/L) for Control, ALA, LDM, HDM and HDM-ALA were as follows; 4.02 ± 0.35, 4.6 ± 0.26, 7.23 ± 0.48, 8.03 ± 0.64 and 4.45 ± 0.41 respectively. After thirty minutes of glucose load (2ug/kg body weight) blood glucose levels were 6.62 ± 0.85, 7.22 ± 0.64, 9.43 ± 1.07, 9.43 ± 1.05 and 7.03 ± 0.52 in the Control, ALA, LDM, HDM and HDM-ALA respectively. Subsequent values were obtained every 30 minutes and after 3 hours, the blood glucose values were 2.32 ± 0.43, 4.26 ± 0.23, 7.29 ± 0.29, 8.28 ± 0.33 and 3.97 ± 0.21 in the Control, ALA, LDM, HDM and HDM-ALA respectively. The results on MDA in the Control, ALA, LDM, HDM and HDM-ALA groups are; 0.0318 ± 0.005, 0.0242 ± 0.004, 0.069 ± 0.004, 0.104 ± 0.011 and 0.045 ± 0.006 respectively. Superoxide dismutase activity was; 46.74 ± 4.85, 43.16 ± 3.68, 24.42 ± 3.17, 19.62 ± 2.51, 35.32 ± 3.38. Reduced glutathione values were; 0.31 ± 0.04, 0.32 ± 0.04, 0.15 ± 0.02, 0.13 ± 0.03, 0.21 ± 0.02 and catalase activity were; 224.60 ± 15.03, 230.98 ± 14.98, 155.11 ± 17.63, 139.38 ± 16.44, 162.94 ± 15.62 in the Control, ALA, LDM, HDM and HDM-ALA respectively (values are in units/mg protein). The results showed changes in glucose tolerance and oxidative indices in rats exposed to HgCl2. However, treatment with ALA attenuated all HgCl2 triggered changes. This study shows the induction of glucose intolerance by HgCl2 and suggests the involvement of oxidative stress as an important regulator of glucose homeostasis during HgCl2 exposure.