We evaluated the effects of high-density stress on gene expression in the intestine, muscle, and brain by measuring Nrf2-Keap1 signaling pathway signaling molecules following different exposure times (30, 60, 90 days) of Megalobrama amblycephala (average initial weight 2.33 g±0.13 g) were reared at two different initial densities (low density group[LD], 534 fish/m³ and high-density group[HD], 1073 fish/m³) for 90 days. At the end of the trial, the results showed that the HD group exhibited increased mRNA levels of Keap1 and Bach1 in the muscle, Bach1 mRNA in the brain, and SOD mRNA in the intestines on day 30 compared to in the LD group. However, the HD group showed significantly decreased mRNA levels of NOX2, Nrf2, and Keap1 in the intestines, NOX2 in the brain, and NOX2, Nrf2, SOD, and CAT in the muscle compared to the LD group. On day 60, the HD group showed increased mRNA levels of NOX, Nrf2, SOD, and CAT in the intestines, NOX and SOD in the muscle, and NOX2, Nrf2, Keap1, Bach1, SOD, and CAT in the brain, but significantly decreased mRNA levels of Bach1 compared to the LD group. On day 90, the HD group showed increased mRNA levels of Nrf2 in the intestines, NOX, Nrf2, Bach1, SOD, and CAT in the muscle, and Nrf2, Keap1, and SOD in the brain, but significantly decreased mRNA levels of Keap1, Bach1, and SOD in the intestines compared to the LD group. Thus, the HD group (1073 fish/m³) in IRAS exhibited increased expression of various stress-related genes in the muscle and brain on day 60. Crowding induced the expression of antioxidant Nrf2-Keap1 signaling molecules to protect the tissues from oxidative stress. However, on day 90, high-density (1073 fish/m³) stress may reduce the mRNA levels of SOD, causing oxidative stress in the intestine and affecting fish growth.