The aim of the article was to evaluate the important role played by insulin in the development of endometrial cancer (EC) among Chinese premenopausal women. In this study, 128 endometrial cancer patients and 294 controls who were all premenopausal were included. Baseline characteristics data were collected and serum insulin, C-peptide, sex hormone-binding globulin, C-reaction protein, interleukin-6, and tumor necrosis factor-α levels were measured. Paired t test, χ2 test, Spearman correlation coefficients, and univariate and multivariate logistic regression models were used in data analysis. Furthermore, insulin levels were categorized into quartiles, and likelihood ratio was calculated for the four categories. Blood insulin levels of the patients were significantly higher than those of the controls (P < 0.001). Factor analysis identified insulin (OR = 2.46; 95 % confidence interval (CI) = 1.55–3.91; P < 0.001) as the independent risk factor of EC. When insulin levels were categorized into quartiles, we found that insulin was positively associated with endometrial cancer risk [HR comparing extreme quartiles (HR q4-q1) = 4.44; 95 % CI = 2.59–7.62; Ptrend = 0.025]. After adjustment for body mass index (BMI) or waist-hip ratio (WHR), this association was attenuated, but still significant. In conclusion, insulin plays an important role in the carcinogenesis of EC among premenopausal women. Treatment targeting down-regulation of blood insulin levels seems effective in the prevention of this malignancy.