Objective Methods Twenty db / db mice aged 4 weeks were randomized to pioglitazone group ( PIO group) and db / db group，fed with 10mg / kg·d pioglitazone and placebo respectively． Ten age-matched db /misty mice were concurrently treated with placebo as non-diabetic control group ( db /m group) ． Body weight and blood glucose were measured every week． After 4 weeks' treatment，the expression of PTP1B in muscle of mice were determined with Western blotting． Results The expression of PTP1B in muscle of db / db mice significantly increased compared with db /m( P＜0. 05) ． Pioglitazone treatment significantly decreased fasting blood glucose and HOMA-IR． The expression of PTP1B in muscle of pioglitazone-treated mice obviously decreased compared with db / db group ( P＜0. 05 ) ． Conclusions Pioglitazone treatment could improve insulin resistance possibly by reducing the expression level of PTP1B in the muscle．