ObjectivesBy comparing with the control group, we evaluated the usefulness of contrast‐enhanced ultrasound (CEUS) combined with elastography for the assessment of muscle invasion by bladder cancer (MIBC) in a Sprague–Dawley (SD) rat model.MethodsIn the experimental group, 40 SD rats developed in situ bladder cancer (BLCA) in response to N‐methyl‐N‐nitrosourea treatment, whereas 40 SD rats were included in the control group for comparison. We compared PI, Emean, microvessel density (MVD), and collagen fiber content (CFC) between the two groups. In the experimental group, Bland–Altman test was used to assess the relationships between various parameters. The largest Youden value was used as the cut‐off point, and binomial logistic regression analysis was performed to analyze the PI and Emean. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic power of parameters, individually and in combination.ResultsThe PI, Emean, MVD, and CFC were significantly lower in the control group than in the experimental group (P < .05). The PI, Emean, MVD, and CFC were significantly higher for MIBC than for non‐muscle‐invasive bladder cancer (P < .05). There were significant correlations between PI and MVD, and between Emean and CFC. The diagnostic efficiency analysis showed PI had the highest sensitivity, CFC had the highest specificity, and PI + Emean had the highest diagnostic efficacy.ConclusionCEUS and elastography can distinguish lesions from normal tissue. PI, MVD, Emean, and CFC were useful for the detection of BLCA myometrial invasion. The comprehensive utilization of PI and Emean improved diagnostic accuracy and have clinical application.