Abstract: Objective To assess the effectiveness of dietary inflammatory index (DⅡ) in pregnant women and the association between DⅡ and serum high-sensitivity C-reactive protein (hs-CRP) in the second trimester of pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A prospective cohort study was conducted at the First Affiliated Hospital of Anhui Medical University for pregnant women. A total of 336 women with singleton pregnancy and without obvious symptoms of infection in 16-20 gestational weeks were enrolled in the study. DⅡ and serum hs-CRP concentration were measured in 16-20 gestational weeks. DⅡ was derived from individual dietary intake obtained by 3 consecutive 24-hour recalls using a validated algorithm. The participants were followed up until delivery and the pregnancy outcomes were recorded. Results A total of 110 observations (32.74% of the total 336 observations) had elevated hs-CRP (>3 mg/L). The risk of developing GDM among women in the elevated hs-CRP compared with the normal hs-CRP was 1.96(95% CI:1.03-3.75). The significant positive relationship was showed between DⅡ and hs-CRP during the second trimester of pregnancy (r=0.20,P=0.003). Three groups were divided according to tertiles of DⅡ. The lowest (most anti-inflammtory) tertile was the referent. The risk of developing GDM increased across the tertiles (i.e., with increasing inflammatory potential):odds ratio (tertile2)=3.66 (95% CI:1.11-12.12); odds ratio (tertile3)=5.99 (95% CI:1.85-19.41). Conclusions The DⅡ is a novel tool that characterizes the inflammatory potential of diet for pregnant women. A higher DⅡ is prospectively associated with a higher risk of GDM, with association with serum hs-CRP. Promotion of a healthy diet exhibiting anti-inflammatory properties may contribute to prevent GDM.