1-Nitropyrene (1-NP) and 1,8-dinitropyrene (1,8-DNP) are nitroarenes commonly found in diesel exhaust and classified as either probable or possible human carcinogens by IARC. Significantly, both compounds require metabolic activation by nitroreduction to generate metabolites capable of forming DNA adducts. Xanthine oxidase (XO) has been identified as one enzyme implicated in the nitroreduction of 1-NP and 1,8-DNP to form DNA adducts in rat liver; however, the enzymes involved in this process in human lung remain to be elucidated. We have previously shown that human aldo-keto reductases (AKR1C1, AKR1C2 and AKR1C3) and NAD(P)H quinone oxidoreductase 1 (NQO1) catalyze the nitroreduction of another diesel exhaust nitroarene, 3-nitrobenzanthrone (3-Nitro-7H-benzo[d,e]anthracen-7-one, 3-NBA), raising the possibility that these enzymes could be involved in the nitroreduction of 1-NP and 1,8-DNP. Furthermore, studies have shown that AKR1C1, AKR1C2 and AKR1C3 are induced by the Nrf2-Keap1 pathway. In the current study, we showed that human recombinant AKR1C1 catalyzed 1-NP nitroreduction using a UV-HPLC-based discontinuous assay that measured the formation of 1-aminopyrene (1-AP), a product of 1-NP nitroreduction. By contrast, AKR1C2 and AKR1C3 catalyzed 1-NP nitroreduction to a more limited extent, while AKR1A1, AKR1B1, AKR1B10, AKR1C4, AKR1C9, AKR1D1, AKR7A2, AKR7A3, and NQO1 had negligible nitroreductase activity with 1-NP as substrate. Investigation of 1,8-DNP nitroreduction showed that AKR1C3 was capable of producing 1-amino-8-nitropyrene (1,8-ANP); however, the reaction failed to go to completion within 24 hours. Other tested enzymes minimally catalyzed 1,8-DNP nitroreduction. Interestingly, our work showed that purified XO catalyzed 1-NP and 1,8-DNP nitroreduction poorly under either aerobic or anaerobic conditions. By contrast, XO catalyzed the robust reduction of cytochrome c. Ongoing work will further elaborate the role of nitroreductases in the metabolic activation of 1-NP and 1,8-DNP in human lung cells.