Purpose Pulmonary fibrosis is a life-threatening lung disorder. A comprehensive understanding of the pathophysiological changes in the development of pulmonary fibrosis will lead to new insights into its treatment. Methods We used a paraquat (PQ)-induced rhesus monkey model of pulmonary fibrosis to comprehensively investigate the process of pulmonary fibrosis development. Rhesus monkeys were orally administered PQ at concentrations of 25 mg/kg, 40 mg/kg, and 80 mg/kg. The dose was given once. Behavior and clinical data, such as PQ concentration, arterial oxygen saturation, biochemical evaluation, lung histopathology, and medical imaging, were continuously observed. Results Paraquat-exposed monkeys developed pulmonary fibrosis following an expected time course, especially at 25 mg/kg. CT images showed ground-glass lesions in the lung after 4 weeks, and pulmonary fibrosis persisted until the end of follow-up. Using pathological examination, the lung sustained collagen deposition and slight inflammatory cell infiltration. All rhesus monkeys had obvious inflammatory infiltration within 1 week according to the immunohistochemical results and the number of leukocytes in the blood. The CT results showed that pulmonary fibrosis had not formed, indicating that drugs with powerful anti-inflammatory ability are potential candidates for early pulmonary fibrosis treatment. Conclusion Our study describes the dynamic process of paraquat-induced pulmonary fibrosis in rhesus monkeys and provided a pathophysiological basis for the treatment of pulmonary fibrosis. Supplementary Information The online version contains supplementary material available at 10.1007/s00408-022-00572-9.