Hematopoiesis in bone marrow declines during aging owing to alteration of the hematopoietic niche. However, due to difficult accessibility and other complexities, senescence-related alteration of the hematopoietic niche is largely unknown. The interstitial fluid of bone marrow (IFBM), a pivotal component of the hematopoietic niche, includes soluble secretory factors that are present between bone marrow cells. To characterize the proteomic profile changes of IFBM during aging, we analyzed the IFBMs of young, adult, and senescent rats using 2-DE combined with ESI/MALDI-Q-TOF MS. Finally, 31 differentially expressed proteins involved in multiple biological functions were identified. Peroxiredoxin 2 (Prx2), down-regulated during aging, was further analyzed and demonstrated that it is produced by bone marrow stromal cells. Interestingly, higher levels of hydrogen peroxide (H(2)O(2)) were detected in the bone marrow with lower Prx2 expression. Moreover, exogenous Prx2 reduced the intracellular H(2)O(2) level in bone marrow stromal cells in vitro. Therefore, Prx2 is implied in the regulation of H(2)O(2) production in the bone marrow during aging. Our data characterized the dynamic protein profiles of the bone marrow microenvironment during aging and we provided clues to elucidate the mechanism of creating a low ROS level in the hematopoietic niche.