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HIGHLIGHTSEffect of Mn exposure on PARK2 gene expression among smelters was studied.Cumulative Mn exposure was significantly higher in smelters than controls.Expression of PARK2 mRNA in smelters was decreased by 42% compared to controls.Expression of PARK2 mRNA was inversely correlated with Mn levels in plasma. ABSTRACT Manganese (Mn) is widely used in modern industries. Occupational exposure to Mn is known to cause clinical syndromes similar, but not identical to, Parkinson's disease. This human cohort study was designed to investigate if workers exposed to Mn altered the PARK2 gene expression, leading to Mn‐induced neurotoxicity. Workers (n = 26) occupationally exposed to Mn were recruited from a Mn‐iron (Fe) alloy smelter, and control workers (n = 20) without Mn‐exposure were from an Fe smelter from Zunyi City in China. Subjects were matched with socioeconomic status and background for environmental factors. Metal concentrations were determined by atomic absorption spectrophotometry (AAS). Total RNA from the blood samples was isolated and analyzed by RT‐PCR to quantify PARK2. The data showed that Mn concentrations in plasma, red blood cell (RBC) and saliva, and the cumulative Mn‐exposure were about 2.2, 2.0, 1.7 and 3.0 fold higher, respectively, in Mn‐exposed workers than those in control subjects (p < 0.01). The expression of PARK2 in Mn‐exposed workers was significantly decreased by 42% as compared to controls (p < 0.01). Linear regression analysis further established that the expression of PARK2 mRNA was inversely correlated with Mn levels in plasma, RBC and saliva, as well as the cumulative Mn exposure (p < 0.01). Taken together, it seems likely that Mn exposure among smelters may lead to a reduced expression of PARK2, which may partly explain the Mn‐induced Parkinsonian disorder.