This study was designed to characterize metabolic responses of meniscal tissue explants to injury and inflammation. We hypothesized that impact injury and interleukin (IL-1β) stimulation of meniscal explants would result in significant increases in matrix metalloproteinase (MMP) activity and relevant cytokine production compared to controls. Mature canine meniscal explants (n = 9/group) were randomly assigned to: (i) IL-1β (0.1 ng/ml) treated (IL); (ii) 25% strain (25); (iii) 75% strain (75); (iv) 25% + IL-1β (25IL); (v) 75% + IL-1β (75IL); or (vi) 0% + no IL-1β control (NC). Explants were impacted at 100 mm/s to 0%, 25%, or 75% strain and then cultured for 12 days with or without 0.1 ng/ml rcIL-1β. Media were refreshed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, GAG, NO, PGE , IL-6, IL-8, MCP-1, and KC concentrations. Treatment with IL-1β alone significantly increased NO, PGE2, general MMP activity, IL-6, IL-8, KC, and MCP-1 media concentrations compared to negative controls. Impact at 75% significantly increased PGE2, IL-6, IL-8, and KC media concentrations compared to negative controls. The combination of IL-1β and 75% strain significantly increased production of PGE2 compared to IL-1β or 75% strain alone. Impact injury to meniscal explants ex vivo is associated with increased production of pro-inflammatory mediators and degradative enzyme activity, which are exacerbated by stimulation with IL-1β. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2657-2663, 2018.