Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load in rats. The NSAID ibuprofen inhibits cyclooxygenase-2 enzyme, effectively reducing loading induced prostaglandin E2. Whether this affects eventual bone mass gains after multiple sessions of a more physiological mechanical loading regimen is unclear. Therefore, the aim of this study was to test the hypothesis that gains in bone mass and size will be diminished in adult rats given ibuprofen before, but not after, each exercise bout during 20 days of simulated resistance training (SRT). Virgin female Sprague-Dawley rats (5-mo-old, n=29) completed 9 SRT sessions using stimulated muscle contractions under anesthesia at 75% peak isometric strength on alternate days; each of 20 contractions included 1 sec isometric + 1 sec eccentric contraction. Animals were blocked assigned by body weight to one of three groups: 1) ibuprofen (30mg/kg) before exercise, placebo after (I:P)(n=9), 2) placebo before, ibuprofen after (P:I)(n=10) and 3) placebo before and after (P:P)(n=10). In vivo pQCT scans measured changes in total volumetric bone mineral density (vBMD) and total bone mineral content (BMC) at the proximal tibia (cancellous), and total vBMD, total BMC and total area at midshaft tibia on days -7 and 21. Dynamic histomorphometry on both midshaft tibiae (exercised and non-exercised legs) determined mineralizing surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR) on the periosteal surface. There were no differences in body weights among groups at baseline or at day 21. There were significant gains due to SRT, but not ibuprofen treatment in total BMC (+10.50 ± S.D. +8.15%) and total vBMD (+5.29 ± 3.41%) at the proximal tibia. The midshaft tibia exhibited significant gains in total vBMD (6.68 ± 3.03%), total BMC (19.18 ± 5.51%) and total area (11.68 ± 5.49%) due solely to SRT. Furthermore, there were significant increases in periosteal BFR (pre 21.89 µm3/µm2/d ±2.63; post 717.81 µm3/µm2/d ±100.57) at the midshaft tibia in the exercised vs. non-exercised legs in all groups but no effect of ibuprofen regimen was detected on these indices of bone formation. In the context of robust increase in BFR and bone mass within this simulated resistance protocol, we were unable to detect any impact of ibuprofen administration on the response to bone loading.