Abstract Objective To observe the effects of hydrochloride pioglitazone on urinary 8-hydroxy-deoxyguanosine (8OHdG) excretion in type 2 diabetics and explore its possible reno-protective mechanisms. Methods Ninety-eight uncontrolled type 2 diabetics were assigned randomly into group DP (pioglitazone add-on) and group DS (sulfonylureas add-on). At the basal and after 12 weeks treatment, FBG, HbA1c, urinary 8-OHdG, urinary albumin(ALB) and urinary creatinine (Cr) were determined, respectively. Results Compared with pre-treatment, FBG, HbA1c and urinary 8-OHdG /Cr ratio(U8CR) were all obviously decreased in both therapy groups; urinary albumin/urinary creatinine ratio(UACR) markedly decreased in group DP (P<0.01), while slightly decreased in group DS (P>0.05) after twelve weeks of observation. After 12-week treatment, UACR and U8CR in group DP were significantly lower than those in group DS (both P<0.05) without no marked difference in FBG and HbA1c between group DP and group DS. Meanwhile, U8CR had positive correlation with UACR (r=0.755, P<0.01). Conclusion Pioglitazone can decrease urinary 8-OHdG excretion and lighten oxidative stress in vivo in type 2 diabetics, which may play a protective role for the kidney damage.