Abstract: Objective To investigate the natural disease course of nonspecific ileocecum inflammation (FNICI) and the possibility of early diagnosis of Crohn’s disease (CD). Methods The patients with an established diagnosis of FNICI at our hospital in the past 4 years were retrospectively analyzed for clinical manifestations, endoscopical, readigraphic and histopathological findings and laboratory data. The patients were followed up regularly for their outcomes. Results Our analysis included 66 patients with FNICI (with a male-to-female ratio of 34∶32 and a mean age of 39 years old). The patients were followed up for 10.5 months on average, and 8 (12.1%) patients developed CD. Among these 8 patients, the initial endoscopic examination upon admission revealed ulcers involving the ileocecum valve, and biopsy results showed focal active chronic mucosal inflammation. Laboratory tests showed that the patients who finally developed CD had significantly higher erythrocyte sedimentation rate (P=0.013) and C reaction protein (P<0.01) than the patients who eventually had full recovery. Conclusion FNICI is a common lesion caused by multiple factors and has not specific endoscopic or histopathological features, which makes its definite diagnosis difficult. The patients with persistent ulcer and elevated erythrocyte sedimentation rate and C reactive protein should be closely followed up for early diagnosis of CD.