Objective: Ankylosing spondylitis (AS) is an immune-mediated chronic disease involving axial joints, peripheral joints and intestines, but the etiology of peripheral knee and intestine has been unknown. This study aimed to study the main pathological changes and mechanisms of knee joint and intestine in cynomolgus monkeys with AS. Methods: Through histomorphological analysis and immunohistochemical experiments, the key characteristics of peripheral knee joint and intestinal tissues of AS were studied and the possible pathogenesis was preliminarily analyzed. Results: The pathological characteristics of peripheral knee joints in AS cynomolgus monkeys mainly showed cartilage erosion on the joint surface, exposed subchondral bone, and jagged joint surface in the early stage. In the late stage, it is mainly manifested as ectopic hyperplasia of cartilage superficial hypertrophy of chondrocytes, and osteophytes are formed through chondroplaginous osteogenesis and fibroogenesis, and cartilage is basically lost. The expression of MMP-3 in cartilage and blood vessels is upregulated, causing cartilage destruction and stimulating angiogenesis. AS cynomolgus monkeys have severe atrophy of small intestinal villi and obvious crypt hyperplasia, and a large number of γδ T cells can be seen in the mucosal intestinal glands of the jejunum and ileum. Conclusion: In this study, the pathological analysis of knee joint and intestine of AS cynomolgus monkey obtained the key characteristics of knee joint and intestinal tissue of this spontaneous model, and proposed a possible pathogenesis. This paper provides new insights into the potential link between autoimmunity in bone tissue and intestinal tissue lesions in AS.