Reference values of erythrocyte sedimentation rate (ESR) are the key to interpret ESR blood test in clinic. The common local reference ESR values are more accuracy in blood test that are established with natural geographical factors by using the multiple linear regression (MLR) model and the artificial neural network (ANN). These knowledge-based methods have limitations since the knowl-edge domains of ESR and natural geographical factors are limited. This paper presents a new cases-depended model to establish refer-ence ESR values with natural geographical factors and location using case-based reasoning (CBR) since knowledge domain of ESR and geographical factors is weak. Overall 224 local normal ESR values of China that calculated from 13623 samples were obtained, and the corresponding natural geographical factors and location that include altitude, sunshine hours, relative humidity, temperature, precipita-tion, annual temperature range and annual average wind speed were obtained from the National Geomatics Center of China. CBR was used to predict the unseen local reference ESR values with cases. The average absolute deviation (AAD), mean square error (MSE), prediction accuracy (PA), and Pearson correlation coefficient (r) between the observed and estimated data of proposed model is 33.07％, 9.02, 66.93％ and 0.78, which are better than those of ANN and MLR model. The results show that the proposed model provides higher prediction accuracy than those of the artificial neural network and multiple linear regression models. The predicted values are very close to the observed values. Model results show significant agreement of cases data. Consequently, the model is used to predict the unseen local reference ESR with natural geographical factors and location. In spatial, the highest ESR reference areas are distributed in the south-west district of China that includes Sichuan, Chongqing, Guangxi and Guizhou provinces, and the reference ESR values are greater than 23 mm/60 min. The higher ESR reference values are distributed in the middle part and north-east of China which include Hubei, Henan, Shaanxi, Shanxi, Jilin and Heilongjiang provinces, and the reference ESR values are greater than 18 mm/60 min. The lowest ESR reference values are distributed in the north-west of China that includes Tibet and Xinjiang, and the reference ESR values are lower than 5 mm/60 min.