Technical Abstract: This study investigated the effects of green tea polyphenols (GTP) and alfacalcidol on bone microstructure and strength along with possible mechanisms in rats with chronic inflammation. A 12-week study using a 2 (no GTP vs. 0.5%, w/v GTP in drinking water) × 2 (no alfacalcidol vs. 0.05 ug/kg alfacalcidol orally, 5x/week) factorial design was employed in lipopolysaccharide (LPS)-administered female rats. A group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Changes in tibial and femoral microarchitecture, and strength of femur were evaluated. Difference in expression of tumor necrosis factor-alpha'(TNF-alpha) in proximal tibia using immunohistochemistry was examined. Compared to the placebo group, the LPS-administered only group had significantly lower femoral mass, trabecular volume, thickness, and number in proximal tibia and femur, and lower periosteal bone formation rate in tibial shafts, while had significantly higher trabecular separation and osteoclast number in proximal tibia, and eroded surface in endocortical tibial shafts. Both GTP and alfacalcidol reversed these LPS-induced detrimental changes in femur, proximal tibia, and endocortical tibial shaft. Both GTP and alfacalcidol also significantly improved femoral strength, while significantly suppressed TNF-alpha expression in proximal tibia. There were significant interactions in femoral mass and strength, trabecular separation, osteoclast number, and TNF-alpha'expression in proximal tibia. A combination of both showed to sustain bone microarchitecture and strength. We conclude that a protective impact of GTP and alfacalcidol in bone microarchitecture during chronic inflammation may be due to a suppression of TNF-alpha.