Objective: To investigate the value on early diagnosis of experimental rat according to computed tomography (CT) combined with the serum level of Serum Soluble Mesothelin-related Proteins (SMRP). Methods: Thirty-two SD rat were divided into three groups, including group A (experimental group) of 20 rats with pleural cavity injection of crocidolite suspension, group B (negative control group) of 6 rats with pleural cavity injection of saline, group C (blank control group) of 6 rats without any processing. Chest and abdominal CT scan and enhancement were performed in the three months and six months after induction and the pleural thickening was analyzed. The serum level of SMRP was measured at the different time period including pre-injection, the post-injection first month, the second month, the third month and the sixth month. The correlation between pleural thickening and serum level of SMRP was analyzed. Results: In group A: 20 cases were performed on CT scan in post-injection third month and we found 13 cases without pleural lesions and 7 cases with pleural lesions including of 4 cases with mild pleural thickening, 1 moderate thickening and 2 severe thickening (2 cases died). Moreover, 18 cases were done by CT in post-injection third month and we found 3 cases without pleural lesions and 15 cases with pleural lesions including of 6 cases with mild pleural thickening, 5 moderate thickening and 4 severe thickening (3 cases died). No pleural lesions were found in group B and group C. SMRP expression level differences in the three groups was statistically significant. However, there was no difference in pre-injection in the three groups and there were no difference in group B and C at the different time period. In group A, there was no difference between post-injection first month and second month, whereas, there had statistically difference in post-injection third and sixth month. In group A, SMRP level gradually increased over time. The high correlation between pleural thickening and serum level of SMRP was seen at the post-injection third and sixth month, which the expression of SMRP gradually increased as the pleural thickening. Conclusion: Serum SMRP expression level has a certain value for early diagnosis and staging of MPM, which can be used as an important biomarker for early screening of high-risk groups exposed to asbestos.