Introduction: Diabetic nephropathy that means albuminuria greater than 30 mg/day, affects about one third of diabetic patients. There are many studies about the effect of different medications for diabetic nephropathy with controversy in their results. So, the aim of the study was to investigate the effect of pioglitazone on decreasing of proteinuria in type II diabetic patients and nephropathy. Methods and materials: It is a double blind clinical trial. At first, 2356 medical carts of the patients were evaluated and 76 patients with type 2 diabetes mellitus with proteinuria greater than 250 mg / day were enrolled in 2 equal groups. In the case group, pioglitazone 15 mg/day was prescribed and patients in the control group received placebo for two months. At the beginning of the study and after 2 months, urinary protein during 24 h was measured in all of the patients and data were entered to SPSS (version23) and evaluated by using Chi- square, Mc Nemar, paired t-test and logistic regression model. Results: At the beginning of the study, urine protein during 24 h in the case and control groups were 957.7 ± 385.1 and 972.1 ± 378.6 respectively (P =.872). So, after 2 months the mean proteinuria in the case and control groups were 647.3 ± 367.2 and 896 ± 372.4 respectively that is valuable (P = 0.005). Pioglitazone had the considerable effect on FBS,HbA1c and blood triglyceride too. Conclusion: The study showed that low dose of pioglitazone is an effective, safe and inexpensive method in reducing of proteinuria in type2 diabetic patients with nephropathy
