To observe the changes of TSP-1 expression in the retina of STZ-induced rat diabetic mellitus model with pioglitazone and to elucidate the possible mechanism involved and the effects of thiazolidinediones compound pioglitazone on the early stages of diabetic retinopathy. 30 Male SD rats were randomly divided into 3 groups: control group, DM group and pioglitazone treated DM group (DP group). DM group and pioglitazone treated DM group were injected with STZ intraperitoneally. 8 weeks after the onset of diabetes, the expression of TSPI mRNA was quantified in retinal tissue by quantitative reverse transcription-polymerase chain reaction (RT-PCR) respectively. The locations of TSP-1 in three groups were also established by immunohistochemistry. 8 weeks after the onset of diabetes, every layer of the retina tissue had significant TSP-1 positive staining and when compared with the control group and DM group, the pioglitazone treated DM group had higher TSP-1 positive cell number per unit area; There were significant differences among the DM group, pioglitazone treated DM group and control group in TSP-1 mRNA level, DM group and pioglitazone treated DM group had significantly higher TSP-1 mRNA level than the control group. Our results showed that pioglitazone treatment can alleviate the pathological changes of DR and the expression level of TSP-1 was increased in pioglitazone treated DM rats compared with other DM rats. Our study suggests pioglitazone may have a role on early stage of DR by increased TSP-1 expression.