Background:Crystalline silica is a commonly used mineral in various industries and construction activities, and it is so important introducing potential biomarkers to identify early indicators of biological effects in its high-risk occupational exposures.Aim:The present study was aimed to assess the blood and urinary neopterin as an early biomarker of exposure in the workers of an insulator manufacturing plant who are exposed to crystalline silica.Subjects and Methods:This analytical descriptive study was done among two groups of exposed workers (n = 55) and unexposed office workers (n = 38) of an insulator manufacturing plant. Statistical software R was used to determine sample size and select the participants by random sampling among nonsmoker workers. Sampling of airborne silica in breathing zone of participants was done based on the National Institute for Occupational Safety and Health method 7601. The urinary and blood samples were collected and prepared for analysis by high-performance liquid chromatography to determine the level of urinary and serum neopterin. All of the statistical analyses were carried out using SPSS 22.Results:The airborne silica concentration was significantly different between two exposed and unexposed groups (P < 0.001, 0.27 [0.11] vs. 0.0028 [0.0006] mg/m3, respectively). The urinary neopterin in exposed group is significantly higher than the unexposed one (P < 0.001, 97.67 [30.24] vs. 55.52 [2.18] μmol/mol creatinine, respectively). Neopterin level of serum in exposed group is higher than the unexposed group, and there is a significant difference between them (P < 0.001, 6.90 [2.70] vs. 2.20 [1.20] nmol/l, respectively). The positive significant correlations were found between silica exposure concentration with urinary and serum neopterin (P < 0.001, r = 0.36 and 0.59, respectively).Conclusions:Considering the sensitively and easily measurement of neopterin in biological fluid and also the statistically significant positive relationships which were found between the airborne silica concentration and neopterin levels in the present study, the serum and urinary neopterin levels can be considered the potential biomarkers of silica exposure for doing further comprehensive studies in this area.