Objective To explore the differential diagnosis value of transrectal ultrasonography (TRUS) signs combined with texture analysis on perianal fistulizing Crohn’s disease (PFCD) and cryptoglandular anal fistula (CAF). Methods The TRUS images of 110 patients with anal fistula were analyzed retrospectively (according to diagnosed medical history divided into PFCD group, n=42; CAF group, n=68), and the TRUS findings of the lesions were compared. The texture features of lesions were extracted by 3D Slicer. TRUS sign models, texture feature models and combined models were constructed with texture features after lasso regression and cross-validation dimensionality reduction screening, and the diagnostic performance of each model was evaluated by ROC curve. Results The combined model screened out four features of Crohn’s Ultrasound Fistula Sign (CUFS), fistula bifurcation, kurtosis, and autocorrelation (p<0.05) with areas under the curve (AUC) of 0.761, 0.676, 0.730, 0.770 respectively. CUFS had the highest specificity at 92.6%. PFCD group had higher kurtosis and autocorrelation than the CAF group (OR=5.1, 5.2, p<0.02). The combined model showed a greater diagnostic efficiency with an AUC of 0.927 (95%CI 0.880~0.974) compared to the TRUS sign model and the texture feature model (p<0.05). Conclusion CUFS is a specific sign of PFCD. High kurtosis and autocorrelation may be characteristic indicators of the textural features of fistulas coexisting with intestinal inflammation. Combining TRUS findings and texture analysis has good differential diagnosis value for PFCD and CAF.