Objectives <p>To explore the quantitative analysis of high <i>b</i> value (2000 s/mm²) diffusion-weighted imaging (DWI) for the differentiation of ileocecal inflammatory conditions and tumors, compared with conventional <i>b</i> value (800 s/mm²) DWI.</p> Methods <p>Sixty-six patients with 30 tumors and 36 inflammatory conditions underwent MR enterography with conventional and high <i>b</i> values DWI. Quantitative apparent diffusion coefficient (ADC) values and signal intensity ratios (SIRs) of lesions of the psoas muscle were measured from the two <i>b</i> value DWIs. The receiver operating characteristic (ROC) curve was applied to determine the diagnostic value of ADC and SIR for differentiating tumors from inflammatory conditions.</p> Results <p>The ADC values of tumors were significantly lower than those of inflammatory conditions in 800 s/mm² (<i>p</i> = 0.001) and 2000 s/mm² (<i>p</i> &lt; 0.001) DWI. In addition, tumors exhibited significantly higher SIR values compared to inflammatory conditions (<i>p</i> &lt; 0.001 in 800 s/mm² and 2000 s/mm² DWI). Areas under the curve (AUC) of ADC and SIR derived from high <i>b</i> value (0.828 for ADC, 0.947 for SIR) were superior to those from conventional <i>b</i> value DWI (0.731 and 0.849, respectively). Compared to ADC, SIR values achieved better AUCs in both two <i>b</i> values DWI.</p> Conclusions <p>Quantitative ADC values and SIR could be used as non-invasive tools to distinguish ileocecal tumors from inflammatory conditions. The use of high <i>b</i> value DWI would improve this ability. Furthermore, SIR obtained from high <i>b</i> value DWI was the most promising quantitative parameter.</p> Critical relevance statement <p>This study indicated that quantitative DWI parameters might be applied as non-invasive imaging biomarkers for distinguishing bowel tumors from inflammatory conditions. The SIR from high <i>b</i> value DWI could improve the differentiation, providing invaluable information for establishing appropriate therapeutic strategies.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Differentiation between bowel inflammatory conditions and tumors is still a dilemma.</p> </ItemContent> <ItemContent> <p>Quantitative DWI contributed to distinguishing ileocecal tumors from inflammatory conditions.</p> </ItemContent> <ItemContent> <p>SIR from DWI is a promising parameter for differentiating these pathologies.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>