Introduction: Diabetes mellitus is metabolic disease and its consequences are seen in many different tissues. Hyperglycemia results in developing reactive oxygen species which induce inflammatory process. The antioxidant capacity of propolis could protect organism from oxidative stress, diminished hyperglycemia effect and could reduce inflammation. Hypothesis: Antioxidant and anti-inflammatory effect of propolis improve life quality and lifespan in alloxan-induced diabetic mice. Methods: Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75 mg kg-1). Two days after alloxan injection, water soluble derivative of propolis (WSDP) or ethanol extract of propolis (EEP) (50 mg kg-1 per day) were intraperitoneally injected for 7 days in diabetic mice. We have measured in vivo lipid peroxidation of liver, spleen, and brain in mice treated with WSDP or EEP. Functional activity of macrophages was also examined and effect of WSDP or EEP on body weight and survival of alloxan-induced diabetic mice. Results: The lipid peroxidation in liver tissue was improved in animals treated by EEP and WSDP (p <0.001). In addition, WSDP was able to lower the extent of lipid peroxidation of kidney and spleen (p <0.05). In our study, we couldn’t observe a difference in malondialdehyde (MDA) levels of diabetic and healthy brain, but in WSDP-treated diabetic animals a significant reduction in MDA levels could be noted. The results showed a statistically significant increase in the number of activated macrophages in untreated diabetic mice and in mice treated with WSDP or EEP (p <0.001) versus healthy animals. Diabetic animals treated with WSDP showed a significantly increased number of functional activated macrophages as compared to untreated diabetic mice (p <0.001). Increased life span was observed in diabetic mice treated with either aqueous or ethanol propolis preparations for 30.43% (WSDP) and 20.67% (EEP), respectively, in relation to control diabetic mice. Conclusions: Our results have shown that propolis preparations have a promising role in the protection against oxidative stress damage in diabetic mice, which may be mainly attributed to its antioxidant and anti-inflammatory potential. The mechanism of polyphenol/flavonoid action on mice with diabetes mellitus is yet to be determined.