Objective To investigate whether 2,3,5,4"-tetrahydroxystilbene-2-O-β-glucoside (TSG) ameliorated polycystic ovary syndrome (PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established by injecting subcutaneously with dehydroepiandrosterone into female Sprague-Dawley rats, followed by receiving intraperitoneal injection of TSG. The granular cells (GCs) KGN were transfected with small interfering RNAs (si-NC and si-CYP19A1). The cells were preincubated with lipopolysaccharide (LPS) and then treated with or without TSG. The estrous cycle was monitored using vaginal exfoliated cells. The morphology of ovarian follicles was analyzed by H&E staining. ELISA was used to analyze estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), IL-6, TNF-α, AGEs, CRP and Omentin-1 levels in serum. Immunohistochemistry was performed to analyze PCNA and CYP19A1 expressions in the GCs of ovaries. Tunel staining was executed to detect the apoptosis of GCs. Quantitative polymerase chain reaction (qPCR) and Western blot were implemented to measure the expression of CYP19A1 in the ovaries and transfected cells. qPCR was used to analyze the expression of IL-6 and TNF-α in the transfected cells treated with LPS and TSG.Results The estrous cycles were restored in TSG group. Compared with model group, the sinus follicles were reduced and corpus luteums were increased in TSG group. TSG group showed increased E2, and decreased T and LH, compared with model group. Pro-inflammatory factors (IL-6, TNF-α, CRP and AGEs) were decreased, and anti-inflammatory factor (Omentin-1) was increased in TSG group compared with those in model group. TSG could partially inhibit decrease of PNCA-positive GCs and increase of Tunel-positive GCs caused by PCOS. The CYP19A1 expression of GCs in TSG group was upregulated compared with model group. The expressions of IL-6 and TNF-α in si-CYP19A1 cells were increased compared with si-NC cells. Compared with cells (si-NC and si-CYP19A1) treated without LPS, the expressions of IL-6 and TNF-α cells were increased, and the expression of CYP19A1 was downregulated in LPS-preincubated cells. Compared with cells treated with LPS, the expression of IL-6 and TNF-α were decreased, and the expression of CYP19A1 was increased in cells treated with LPS and TSG. Compared with si-NC cells treated with LPS and TSG, the expressions of IL-6 and TNF-α cells were increased in the si-CYP19A1 cells treated with LPS and TSG.Conclusion TSG could alleviate PCOS-like characteristics by increasing the expression of CYP19A1 in GCs to inhibit inflammatory response.