Objective:To study the correlation of Sema3A/Nrp1 pathway in gingival crevicular fluid of chronic periodontitis with inflammatory response and bone destruction. Methods: A total of 49 patients who were diagnosed with chronic periodontitis in the First People's Hospital of Jiangxia District, Wuhan City between July 2014 and January 2017 were selected as CP group, and 55 volunteers who received physical examination during the same period and had complete dentition were selected as control group. Gingival crevicular fluid was collected to detect the protein levels of Sema3A/Nrp1, inflammatory response indexes, bone metabolites and bone metabolism molecules. Results: Sema3A, Nrp1, PICP, Wnt1, β-catenin, and OPG protein levels in gingival crevicular fluid of CP group were significantly lower than those of control group while YKL40, CXCL16, ICAM1, HMBG1, SDF1α, ICTP, NTX, CTX, RANKL, 5-LOX and LTB4 protein levels were significantly higher than those of control group; Sema3A and Nrp1 protein levels in gingival crevicular fluid of CP patients were negatively correlated with YKL40, CXCL16, ICAM1, HMBG1, SDF1α, ICTP, NTX, CTX, RANKL, 5-LOX and LTB4 protein levels, and positively correlated with PICP, Wnt1, β-catenin and OPG protein levels. Conclusion: The inhibition of Sema3A/Nrp1 pathway in gingival crevicular fluid of chronic periodontitis can aggravate inflammatory response and promote bone destruction.