Objective. Simiao pill (SM), a traditional Chinese formula, has been used as an antirheumatic drug in clinical practice for hundreds of years. Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia, cartilage destruction, and joint damage. This study was designed to investigate the protective effects of SM on collagen-induced arthritis (CIA) in rats. It also aimed to explore whether this protective effect of SM was related to the inhibition of the ATX-LPA and MAPK signalling pathways. Materials and Methods. Rats were injected with a collagen II emulsion at the end of the tail and on the back to induce arthritis. Treatment with different doses of SM was conducted by intragastric administration. Then, body weights and arthritis scores were measured. The serum levels of tumour necrosis factor (TNF)-, interleukin (IL)-1, C-reactive protein (CRP), osteoprotegerin (OPG), autotaxin (ATX), and lysophosphatidic acid (LPA) were determined by ELISA. Pathological changes in the joints were measured by micro-CT and assessed via haematoxylin-eosin (H&E) staining. The expression of ATX, LPA receptor 1 (LPA1) was detected by immunohistochemical staining, and the expression of mitogen-activated protein kinase (MAPK) was detected by Western blotting. Results. SM significantly alleviated arthritis symptoms, inhibited bone erosion, and decreased the levels of TNF-, IL-1, CRP, ATX, and LPA in the sera of CIA rats. Importantly, SM clearly reduced the protein expression of LPA1 and ATX. The activation of the MAPK signalling pathway was also inhibited by SM in the synovial tissues of CIA rats. Conclusions. The antirheumatic effects of SM were associated with the regulation of the ATX-LPA and MAPK pathways, the suppression of proinflammatory cytokine production, and the alleviation of cartilage and bone injury. These findings suggest that SM might be a promising alternative candidate for RA therapy.