<p>Background: Embryo implantation is a critical and multifactorial phenomenon which can be affected by any alteration in molecular micro construction of endometrium. The aim of the current study was to evaluate the effects of diabetes on osteopontin (OPN) and &alpha;3&beta;1 integrin proteins level at the time of endometrial receptivity.<br /> Methods: Twenty-eight female rats were divided into control, diabetic, pioglitazone-treated and metformin-treated groups. Western blot was performed to determine the OPN and &alpha;3&beta;1 integrin proteins in rats&rsquo; endometrium at the time of implantation. Data were analyzed by analysis of variance (ANOVA) and p&lt;0.05 was considered statistically significant.<br /> Results: OPN increased significantly in the diabetic group in comparison with control (p&lt;0.001), metformin-treated (p=0.008) and pioglitazone-treated groups (p&lt;0.001). Furthermore, &alpha;3&beta;1 integrin protein level in diabetic group had a significant difference in comparison with that of the control (p&lt;0.001), metformin-treated (p=0.026) and pioglitazone-treated groups (p&lt;0.001).<br /> Conclusion: OPN and &alpha;3&beta;1 integrin proteins are involved in embryo implantation and their changes in diabetic condition can affect fertility. Treatment with pioglitazone and metformin improved the level of OPN and &alpha;3&beta;1 integrin proteins while pioglitazone was more effective.</p>