The present study aimed to investigate the histological changes caused by neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC), and to demonstrate the use of time‑density curves (TDCs) of dynamic contrast‑enhanced computed tomography (CECT) for determination of the histological therapeutic effects of NAC for PDAC. A total of 96patients with PDAC were examined; 46 underwent NAC (NAC group) and 50 did not undergo NAC (non‑NAC group). Based on histological therapeutic effect and using the area of residual tumor (ART) grading system, the NAC group was divided into low‑responders and high‑responders. Histological analysis was used to evaluate the densities of cancer cells, cancer‑associated fibroblasts (CAFs), microvessels and stromal collagen fibers in the NAC and non‑NAC groups. Radiological analysis was used to evaluate the TDCs of three slopes of the NAC group, namely slopes between the non‑contrast and arterial phases (δ1 and δ1'), between the arterial and portal phases (δ2 and δ2'), and between the portal and equilibrium phases (δ3 and δ3'). δ1‑δ3 were before NAC, whereas δ1'‑δ3' were after NAC. Changes in δ1, δ2 and δ3 before and after NAC were denoted as δδ1 (=δ1'‑δ1), δδ2 (=δ2'‑δ2) and δδ3 (=δ3'‑δ3). ART grading system, histological examination and radiological examination data were also statistically analyzed. Histological examination revealed a significant decrease in cancer cells and CAFs, and a significant increase in stromal collagen fibers due to NAC (P<0.01). Radiological examination revealed that δ1' was significantly higher than δ1 in low‑responders (P<0.05), whereas δ2' was significantly lower than δ2 in high‑responders (P<0.01). δδ2 was significantly lower and δδ3 was significantly higher in high‑responders than in low‑responders (P<0.01 and P<0.05, respectively). Receiver operating characteristic curve showed that δδ2 and δδ3 were effective indicators of the histological therapeutic effect of NAC. In conclusion, the TDC of dynamic CECT may be useful for determining the histological therapeutic effect of NAC for PDAC.