Abstract Objectives The present study aimed to explore the relationship of circulating vaspin levels with insulin sensitivity and anthropometric factors. Methods This study was conducted with 65 newly diagnosed type 2 diabetes mellitus (T2DM) patients with age-matched 65 healthy controls. Serum glucose was measured using glucose-oxidase method, lipid profiles by enzymatic end-point methods, and fasting insulin and vaspin levels were assessed with ELISA techniques. Homeostasis model assessment for insulin sensitivity (HOMA%S) and insulin secretory capacity (HOMA%B) were estimated from the fasting glucose and insulin levels using HOMA-CIGMA software. Results Fasting serum insulin (μU/ml) was higher in the diabetic group than controls (16.0 ± 7.9 vs. 10.9 ±3.3, respectively, p =0.0001). The mean (±SD) HOMA%S of the diabetics was significantly lower than that of the controls (48 ±31 vs. 76±55, respectively, p = 0.001). The HOMA%B of the T2DM group was nearly 50% of that of the controls (71± 40 vs. 131 ±46, respectively, p = 0.001). The T2DM group exhibited significantly lower serum vaspin (ng/ml) levels than the controls (0.62 ±0.26 vs. 0.83± 0.28, respectively, p =0.001). Vaspin levels were negatively correlated with waist circumference (r =0.17, p =0.043) and positively correlated with HOMA%S (r =0.243, p =0.007) among all of the participants. The association of serum vaspin with diabetes remained highly significant (p =0.008) in binary logistic regression analysis performed after adjusting for the effects of confounders. Conclusions Serum vaspin level is positively associated with insulin sensitivity and negatively correlated with serum glucose, BMI and waist-height ratio.