Objective To explore the relationship between serum lactate dehydrogenase (LDH) and insulin resistance in patients with type 2 diabetes mellitus (T2DM). Methods A total of 138 T2DM inpatients admitted in our department from October 2016 to December 2017 were enrolled in this study. After admission, the patients received oral glucose tolerance test (OGTT), i.e. 75g of glucose was taken orally in the early morning under fasting condition. The blood glucose and insulin levels were measured before and 30,60 and 120min after oral taking. According to homeostasis model assessment of insulin resistance (HOMA-IR), the patients were divided into HOMA-IR＜2.5 group (n=50) and HOMA-IR≥2.5 group (n=88). Their general data, related biochemical indices, LDH and Matsuda insulin sensitivity index (ISI) were collected and compared between the 2 groups. According to LDH level, they were divided into 3 subgroups (<172,172-197, and >197IU/L). The related indices of β cell function (HOMA-IR and Matsuda ISI) and other indices were compared among the 3 subgroups. SPSS statistics 24.0 was used for data analysis. According to the type of data, independent sample t test, Mann-Whitney U test, Chi-square test, one-way ANOVA or Kruskal-Wallis H test was employed for the comparison in the groups. Spearman nonparametric correlation analysis was applied for index correlation. Multivariate logisticregression analysis was performed to evaluate the risk factors for insulin resistance. Results Compared with the HOMA-IR<2.5 group, the levels of LDH, fasting blood glucose, and insulin at every time point were significantly higher, while Matsuda ISI was obviously lower in the HOMA-IR≥2.5 group (all P<0.05). The percentage of the patients with HOMA-IR≥2.5 accounted for 50.00%(23/46), 52.17%(24/46) and 89.13%(41/46), respectively, in the 3 subgroups of LDH levels in order. With the increase of LDH levels, HOMA-IR was notably increased, Matsuda ISI was markedly decreased, and the insulin levels were different at different time points in the 3 subgroups (P<0.05). Correlation analysis showed that LDH was positively correlated with HOMA-IR (r=0.289,P<0.05), and negatively with Matsuda ISI (r=-0.314, P<0.001). After adjustment for age and other related factors, multivariate logistic regression analysis showed that LDH was one of the independent predictors of insulin resistance (OR=2.99,95%CI 1.83-4.67; P<0.001). Conclusion LDH has significant correlations with HOMA-IR and Matsuda ISI, which can be used as a simple index to evaluate the severity of insulin resistance in T2DM patients and help to adjust the treatment regimen.