BACKGROUND Preclinical and clinical studies have shown that the extract of Cynanchum paniculatum (bunge) kitag and the fukeqianjin formulation have beneficial effects in pelvic inflammatory disease (PID). This study aimed to compare the effects of Cynanchum paniculatum and fukeqianjin with a new decoction, xiaoyuningkun, consisting of Melia toosendan, Angelica biserrata, and Cynanchum paniculatum, in a mouse model of PID. MATERIAL AND METHODS The mouse model of PID included injection of the upper genital tract with hydrochloric acid (HCl) and lipopolysaccharide (LPS). The control group underwent sham treatment with 0.9% physiological saline. Cynanchum paniculatum, fukeqianjin, and xiaoyuningkun decoction were administered orally for 15 days. Acetic acid-induced writhing and thermal nociception hot plate tests evaluated the analgesic effects of treatment. Mouse uterus and Fallopian tubes were examined histologically to evaluate the degree of inflammation. Immunohistochemistry was used to measure the protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF). Enzyme-linked immunosorbent assay (ELISA) measured serum levels of inflammatory cytokines. RESULTS Treatment with xiaoyuningkun decoction significantly reduced the pain threshold in the mouse model of PID and the degree of inflammation in the uterus and Fallopian tubes compared with Cynanchum paniculatum and fukeqianjin. Cynanchum paniculatum decoction significantly reduced the serum levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-alpha), ICAM-1, and VEGF, and the expression of ICAM-1 and VEGF in the mouse uterus and Fallopian tubes. CONCLUSIONS The new xiaoyuningkun decoction had analgesic and anti-inflammatory effects in the mouse model of PID, possibly by inhibiting ICAM-1, VEGF, and inflammatory cytokines.