Abstract: Objective To establish a SD rat model of vulvar lichen simplex chronicus (LSC) and investigate the expression of protease activated receptor 2 (PAR2) in the genital skin. Methods Seventy female SD rats were randomly divided into group A (blank control group, n=10), group B (with application of acetone solution 3 times per week for 10 weeks, n=10), group C (with chronic mechanical irritation 3 times per week for 10 weeks, n=10), and group D (with topical treatment with 0.5% 7, 12-Dimethylbenzanthracene [DMBA] in acetone solution and chronic mechanical irritation 3 times per week for 10 weeks, n= 40). The changes of the genital skin changes were observed regularly and the expression of PAR2 in groups A and D was detected with immunohistochemistry, Western blotting and qRT-PCR. Results In group D, LSC occurred in 23 rats (57.5%) at 8 weeks and in 38 rats (95%) at 10 weeks; 8 rats (20%) showed papilloma at 12 weeks. Acetone treatment or chronic mechanical irritation did not cause LSC in the rats. Immunohistochemistry, Western blotting and qRT-PCR showed significantly increased expressions of PAR2 in group D at both the protein and mRNA levels as compared with those in group A (P<0.05). Conclusion 0.5% DMBA in acetone solution along with chronic mechanical irritation can induce LSC in female SD rats, and PAR2 is closely related with the occurrence and progression of LSC.