Objective To analyze the correlation of serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), lysophosphatidic acid (LPA) and D-dimer with deep venous thrombosis (DVT) after lower limb fracture, and to explore their roles and underlying mechanism in the formation. Methods A total of 156 patients with lower limb fracture admitted in our hospital were enrolled in this study. According to whether DVT occurred after operation, they were divided into DVT group (n=44) and non-DVT group (n=112). The serum levels of hs-CRP, IL-6, LPA and D-dimer were monitored at 1 d before and in 1,3 and 5 d after operation. SPSS statistics 19.0 was used for statistical analysis. The receiver operating characteristic (ROC) curve was used to analyze the values of hs-CRP, IL-6, LPA and D-dimer in the diagnosis of DVT at various time points after operation. Pearson correlation analysis was employed to analyze the correlation among above indicators. Results The serum levels of hs-CRP, IL-6, LPA and D-dimer at 1,3 and 5 d after operation were significantly higher in the DVT group than in the non-DVT group (P<0.05). In the DVT group, the levels of these indicators were notably increased with time elapsing after operation (P<0.05). While in the non-DVT group, the levels on the 5th day were obviously lower than those on the 1st and 3rd days (P<0.05). The ROC curve analysis showed that the area under ROC curve (AUC=0.961,5%CI 0.896-0.994) for DVT diagnosis when the 4 indicators were combined together was the highest on the 3rd day after operation, with sensitivity of 96.8% and specificity of 90.2%. In the test of single indicator, the level of D-dimer on the 3rd day was best for DVT diagnosis with AUC of 0.892(95%CI 0.833-0.952), and sensitivity of 84.6% while specificity of 87.3%. Correlation analysis indicated that the hs-CRP level was well correlated with that of D-dimer on the 3rd day after operation in the DVT patients (r=0.826, P<0.001). Conclusion hs-CRP, IL-6, LPA and D-dimer are good indicators to predict the formation of DVT, and the value of combined diagnosis of DVT is quite higher on the 3rd day after operation.