Available online A B S T R A C TAdipose tissue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. Hypoadiponectinemia contributes to the development of obesity and related disorders such as diabetes, hyperlipidemia, and cardiovascular diseases. In this study, we investigated the effects of Brazilian propolis on adiponectin levels in type 2 diabetes mellitus (T2DM), the mechanism of signaling pathway was explored as well. T2DM was induced in male Wistar rats using high fat diet and low dose of streptozotocin (STZ, 35 mg/kg, i.p.).Propolis was administered by oral tubes. Peroxisome proliferator activated receptor gamma (PPARγ) levels in sub abdominal adipose tissue, serum levels of adiponectin, tumor necrosis factor-α (TNF-α) and insulin were detected by Enzyme Linked Immunosorbent Assay (ELISA).Malondialdehyde (MDA) and reduced glutathione (GSH) in sub abdominal adipose tissue, fasting plasma glucose, plasma triglycerides and total cholesterol levels were measured by colorimetric method. Results showed that Brazilian propolis ameliorated hypoadiponectinemia in T2DM rats and relieved high glucose-induced adiponectin decrease. The signaling pathway analysis indicated that PPARγ regulation was involved. In conclusion, Brazilian propolis could have beneficial effect in T2DM by increasing tissue PPARγ levels, restoring serum adiponectin levels, enhancing insulin sensitivity and subsequently, attenuating elevated glucose level.