Objective: To investigate the value of combining multiple parameters of trans-rectal ultrasonography (TRUS) to assess the efficacy of neoadjuvant radiotherapy (NCRT) for locally advanced rectal cancer (LARC)，and compare it with magnetic resonance tumor regression grade(mrTRG). Methods: Data were collected on 96 patients with LARC who underwent total mesenteric resection (TME) after NCRT. According to the pathological tumor regression grading (pTRG), patients were divided into good response group (pTRG 0 and 1, 34 cases) and poor response group (pTRG 2 and 3, 62 cases). Clinical and ultrasound data before and after treatment were collected, including the age, sex, CEA, CA199 of the patient and distance from the lower edge of the tumor to the Hilton line (Intersphincteric Groove), long diameter and thick diameter of the tumor, the peak systolic velocity (PSV) of the major arteries within the tumor, the resistance index (RI), and the contrast enhanced ultrasound inhomogeneity grade of the tumor (CEUS-IG). The differences in ultrasound parameters between the two groups were compared, and the parameters that differed between the groups were analyzed by binary logistic regression to establish a multi-parameter prediction model and their predictive efficacy were compared with mrTRG. Results: Before NCRT, the differences of all ultrasound parameters between the two groups were not statistically significant (p>0.05); after NCRT, the differences of CEUS-IGpost, tumor long-diameter change rate, PSV change rate, and downgrade of CEUS-IG (ΔCEUS-IG) were statistically significant in the two groups (p<0.05); the differences in the remaining clinical and ultrasound parameters between the two groups were not statistically significant. The cut-off values of tumor length diameter change rate and PSV change rate were 26.0% and 22.5%, and the accuracy were 63.50% and 68.75%, respectively; The accuracy of ΔCEUS-IG was 71.90%, which was lower than that of mrTRG (83.33%, p<0.05); the accuracy of CEUS-IGpost in predicting pTRG was 83.30%, which was comparable to that of mrTRG (p>0.05). The accuracy of the established regression prediction model was 84.4%, with an AUC of 0.917, and its accuracy was not statistically significant (p>0.05) from both CEUS-IGpost and mrTRG. Conclusion: Parameters CEUS-IGpost, tumor length-diameter change rate, PSV change rate, and ΔCEUS-IG after NCRT could be used to distinguish the good response group and the poor response group of NCRT, and the multi-parametric ultrasound may have comparable value of applications with mrTRG in assessing the efficacy of rectal cancer after NCRT.