Objective Ankylosing spondylitis (AS) is an immune-mediated chronic disease involving axial joints, peripheral joints, and intestines, but the etiology of peripheral knees and intestines is unknown. This study examined the main pathological changes and mechanisms of knee joints and intestines in cynomolgus monkeys with AS. Methods The main characteristics of peripheral knee joint and intestinal tissues of AS were examined and the possible pathogenesis was preliminarily analyzed by histomorphology and immunohistochemistry. Results The pathological characteristics of peripheral knee joints in AS cynomolgus monkeys were mainly cartilage erosion on the joint surface, exposed subchondral bone, and a jagged joint surface in the early stage. In the late stage, the knee joints mainly manifested as ectopic hyperplasia of cartilage superficial hypertrophy of chondrocytes, osteophytes formed through chondrogenesis and fibrogenesis, and loss of cartilage. MMP-3 expression in cartilage and blood vessels was upregulated, causing cartilage destruction and stimulating angiogenesis. AS cynomolgus monkeys had severe atrophy of small intestinal villi and obvious crypt hyperplasia, and a large number of γδT cells was seen in the mucosal intestinal glands of the jejunum and ileum. Conclusions Pathological analysis of knee joints and intestines in AS cynomolgus monkeys revealed their main characteristics in this spontaneous model and suggested the possible pathogenesis. This study provides new insights into the potential link between autoimmunity in bone tissue and intestinal tissue lesions in AS.