Objective To explore the changes of adiponectin (APN) and leptin in patients with type 2 diabetes mellitus (T2DM), the relationship with urinary albumin excretion rate (UAER) and the role in leptin resistance. Methods The levels of plasma leptin, APN and UAER in high-risk T2DM patients before and after pioglitazone treatment were determined by RIA, ELISA and automatic biochemistry analyzer respectively. Results The leptin levels in DM and DN group were higher than that of normal group (p < 0.01), and it gradually increased as the disease progresses. The leptin levels was positively related with urinary albumin excretion rate (r = 0.292, p < 0.05). The APN levels in DM and DN group were lower than that of normal group (p < 0.01), and it gradually increased as the disease progresses. The APN levels was positively related with urinary albumin excretion rate (r = 0.284, p < 0.05). The levels of urinary albumin and plasma leptin in DN group patients after pioglitazone treatment were decreased, while the APN levels were relatively increased. Conclusion The higher leptin and UAER with lower APN are related with the occurrence and development of DM and DN. The pioglitazone has certain role in improvement of insulin and leptin resistance and may have positive significance for guiding the treatment of patients with diabetes.