Reactive oxygen species (ROS) have been implicated in the development of psychiatric disorders. We presently report NOX1/NADPH oxidase regulates the emotional behavior demonstrated in chronic pain model as well as maternal immune activation (MIA) model. There was no difference in the mechanical allodynia developed by spared nerve injury between Nox1 deficient mice (NOX1-KO) and wild type mice (WT). Increased anxiety- and depressive-like behaviors in WT by chronic pain were markedly ameliorated in mice deficient in NOX1-KO. Similarly, the impaired recognition by chronic pain demonstrated in WT was significantly suppressed in NOX1-KO. These affective and cognitive impairment were ameliorated in mice selectively suppressed the expression of hippocampal NOX1 mRNA. In MIA model of gestational polyinosinic-polycytidylic acid, increased serum levels of IL-6 were observed in both genotypes, however, impairment of social preference and defects in motor coordination were observed in WT but not in NOX1-KO. MIA up-regulated NOX1 mRNA in the cerebral cortex and cerebellum of the fetus but not in the offspring. The dropout of Purkinje cells in lobule VII of MIA-affected offspring was significantly ameliorated in NOX1-KO. Taken together, NOX1 may therefore play a key role in the development of behaviors related to the psychiatric disorders.