Objective: To investigate the spectrum distribution and prognosis of patients with terminal ileum lesions, and to explore the diagnostic value of clinical, endoscopic features and peripheral blood indexes in the etiology of the disease. Methods: This study was a retrospective study, including patients who underwent colonoscopy and found terminal ileum lesions in Jiangsu Province Hospital from January 2014 to June 2021. General information, medical records, endoscopy and pathological reports of the patients were collected, and clinical and endoscopic characteristics and etiological diagnosis were statistically analyzed. The patients with CD and non-specific terminal ileum ulcer were screened, and the clinical and endoscopic characteristics and peripheral blood indexes of the two groups were compared. Results: A total of 956 patients with terminal ileal lesions were included, 93 of whom had a clear diagnosis, including CD, intestinal tuberculosis, benign tumors, adenocarcinoma, etc., 425 were lost to follow-up, and another 438 patients with unknown causes. Among the patients with unknown diagnoses, 293 had a repeat colonoscopy, and 182 of them showed that the lesions disappeared. Finally, 22 patients with CD and 73 patients with non-specific terminal ileal ulcer were screened out. Compared with the latter, patients with CD have a higher incidence of abdominal pain at initial diagnosis and are more likely to show endoscopic features of ileocecal valve involvement. Peripheral blood inflammation-related indicators such as platelets, hemoglobin, albumin, platelet/lymphocyte ratio, and neutrophil/lymphocyte ratio have certain value in assisting in the diagnosis of CD. The combined diagnostic value of the five indicators is higher, with an area under the curve of 0.83. Conclusion: Most terminal ileal lesions are non-specific benign lesions and have a good prognosis. For patients whose terminal ileal lesions, especially ulcers, are first discovered under colonoscopy, attention should be paid to their clinical symptoms and endoscopic characteristics, and combined with changes in peripheral blood inflammation-related indicators, it is helpful to diagnose the cause of terminal ileal lesions.