To investigate the causes of transient decrease of spleen density under MSCT and its correlation with C-reactive protein (CRP). Methods Twenty cases of transient decrease of spleen density in our hospital from September 2016 to April 2021 were analyzed retrospectively, including 19 cases of MSCT plain scan and 1 case of MSCT plain scan+enhanced scan. The clinical manifestations of different diseases and related laboratory examinations as well as the changes of spleen density were analyzed. Results Among the 20 cases, 12 cases of acute pancreatitis (AP), 6 cases of tumor after operation, and 2 cases of pneumonia. All the 20 cases of spleen density decreased diffusely, with an average CT value of (12.88±6.69)HU. After treatment, the spleen density recovered / increased with an average CT value of (42.61±3.97)HU. CRP increased in different degrees before treatment, with an average of (211.03±106.70)mg/L, and decreased significantly in 18 patients after treatment with an average of (27.89±23.73) mg/L, another 2 cases were not check CRP. There were significant differences in spleen density and CRP before and after treatment (P＜0.05). There was a negative correlation between spleen density and CRP before and after treatment, and the correlation coefficients were -0.736 and -0.488, respectively (P＜0.05). Conclusion The transient decrease of spleen density is caused by a variety of causes, which is closely related to the inflammatory response mediated by inflammatory factors. It is of great significance to determine the severity and prognosis of the disease