[Abstract] Objective To investigate the effect of Paeonol (Pae) on pathological changes of achilles tendon and synovium in ankylosing spondylitis (AS) mouse model by regulating p38MAPK signaling pathway.Methods Forty-eight SD rats were randomly divided into Sham group, AS group, AS + positive drug group and AS + Pae group (n = 12).The AS model was established by injection of complete Freund's adjuvant.The AS + positive drug group was administered intragastrically with sulfasalazine (9 mg·kg?1·d ?1).The AS + Pae group used Pae intragastric intervention (3 mg·kg?1·d ?1). The serum TNF-α, microstructure of the sacroiliac joint synovium, ossification of Achilles tendon tissue and p38MAPK pathway were detected by ELISA, TEM, HE staining and Western blot, respectively. Results After intervention, TNF-α in AS group was significantly higher than that in Sham group (P <0.05).The TNF-α of AS + positive drug group and AS + Pae group was significantly lower than that of AS group (P <0.05).Synovial cells in the AS group were disorderly arranged, the thickness of the intracellular membrane increased significantly, the cytoplasm was unevenly distributed, and the organelles were abnormal.The synovial microstructure damage in the AS + positive drug group and the AS + Pae group was lighter than that in the AS group.Compared with the Sham group, inflammatory infiltration, fibroid infiltration, and partial cartilage formation were observed in the AS group, and the ossification score of the AS group was significantly higher than that of the Sham group (P <0.05).The AS + positive drug group and AS + Pae group had only inflammatory infiltration and partial fibrous infiltration, and the ossification score was significantly lower than that in the AS group (P <0.05).The levels of p-MKK3 / 6 / MKK3 / 6 and p-p38 / p38 in the AS group were significantly higher than those in the Sham group (P <0.05).The levels of p-MKK3 / 6 / MKK3 / 6 and p-p38 / p38 in AS + positive drug group and AS + Pae group were significantly lower than those in AS group (P <0.05).ConclusionPae can inhibit the synovial cell damage, inflammatory reaction of Achilles tendon and ossification of AS model rats by regulating the p38MAPK pathway, thereby playing a role in treating AS.