Senile osteoporosis (SOP) is a degenerative bone disease associated with increasing susceptibility to fractures and mortality in the elderly. Innate immunity and specifically the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, with its subsequent mediators caspase1- and interlukin-1b (IL-1b), have recently been linked to osteoporosis. Probiotic lactobacillus acidophilus (L.A) was reported to exert favorable effects on osteoporosis. The aim of this study was to identify the protective effects of probiotic L.A in aged osteoporotic rat model and to evaluate the possible underlying mechanisms focusing on NLRP3 inflammasome and its effectors caspase-1 and interleukin -1b. Thirty-two adult male albino rats were designated to four equivalent groups. Group I; control, group II; probiotic L.A, group III; osteoporotic group, and group IV; probiotic LA+ osteoporosis group. Osteoporotic rats pretreated with L.A in a dose of 109CFU/ml / day for 8 weeks revealed a significantly lower oxidative stress state, increased bone mineral density (BMD), enhanced bone histological architecture, lower serum calcium, higher bone formation markers associated with lower bone resorption marker, lower serum receptor activator of nuclear factor kappa-Β ligand (RANKL), decreased bone NLRP3 inflammasome as well as caspase-1 expression levels and lower serum IL-1b. Osteoprotective effects of probiotic L.A in SOP rat model mediated even in part via its anti-inflammatory effects that were represented by decreased NLRP3 inflammasome and its subsequent mediators caspase-1 and IL-1b, that resulted in enhancement of bone formation and reduction of bone resorption.