Abstract Background As a non-invasive, accurate, and feasible examination, transabdominal ultrasound(TAUS) is of great value in disease monitoring of ulcerative colitis. The cut-off for disease activity of 3.0 or 4.0 mm is often debated, and studies lacked assessment of treatment response. This study aimed to assess the diagnostic accuracy of TAUS in detecting disease activity in adult patients with UC using endoscopy as the reference standard and evaluate TAUS for treatment response in a longitudinal cohort. Methods This study prospectively consecutive adult patients with an established diagnosis of UC in the First Affiliated Hospital of Zhengzhou University between June 2022 and September 2023. The patients with moderate-to-severe disease activity at baseline should have follow-up endoscopic assessment after induction, with available corresponding TAUS. The primary outcome of this study was the difference in BWT in the descending colon(DC) or sigmoid colon(SC) for patients with and without segmental endoscopic response after treatment. Endoscopic remission was defined as MES=0-1 or UCEIS=0-1, and Endoscopic response as a decrease of MES ≥1 or a reduction of UCEIS ≥2. Results A total of 315 colon segments in 80 patients were included. 171 (54.3%) colorectal segments had endoscopic remission and 144(45.7%) were in endoscopic activity. The TAUS parameters correlated with the Mayo endoscopic sub-score with significant differences between patients in endoscopic remission and patients in endoscopic activity. And we found 3.45mm(AUROC 0.833;95%CI 0.789-0.878, P<0.001) to be the cutoff for endoscopic remission with 78% sensitivity and 75% specificity. The multivariable analysis identified BWT, the Colour Doppler Signal(CDS), and the wall layer stratification as independent predictors for endoscopic activity( P<0.001、=0.004、=0.001). BWT in the DC or SC was significantly lower in patients with endoscopic response than those without after treatment. A 28% decrease in BWT from baseline predicted endoscopic response [AUROC 0.743;95%CI 0.589-0.896, P=0.015] with 58% sensitivity and 93% specificity. Multivariable analysis among all the ultrasound parameters considered normal wall layer stratification at baseline as the only independent predictor of endoscopic response at reassessment (odds ratio [OR]23.334, 95% CI 2.257-241.219; p = 0.008). Conclusion TAUS, importantly BWT, CDS, and wall layer stratification as the crucial parameters, is highly accurate in detecting disease activity and treatment response when evaluated against endoscopic outcomes. Normal intestinal wall stratification at baseline predicts long-term endoscopic response.