Low oral bioavailability of calcium leads to impairment of calcium homeostasis particularly during the high requirement phases of human growth. The objective of the current study was to prepare microspheres of calcium using bovine serum albumin and assess its viability to enhance the oral bioavailability. Microspheres of calcium were prepared by emulsion chemical cross linking method, characterized, evaluated for in vitro release and in vivo absorption. The prepared microspheres were found to be spherical in shape with smooth surface. High entrapment efficiency (>50%), desired particle size (<10 µm), high zeta potential values (-30.91 ± 3.06 to -34.65 ± 1.01 mV) and low polydispersity indices (0.61 ± 0.04 to 0.88 ± 0.05) were recorded in the prepared microspheres. In vitro release profile suggests that <10% of calcium was discharged in the gastric media (in 30 min) from the microspheres prepared using higher drug/polymer ratio (1:1, formulation F4). The pharmacokinetic data obtained in Sprague-Dawley rats showed that the rate and extent of calcium absorption was significantly enhanced following the administration of microspheres. The serum calcium level profiles indicate that the C(max) and AUC(0-α) were significantly higher (p < 0.001) when calcium was administered from microspheres when compared to control. Rapid absorption of calcium was also observed from microspheres and may be attributed to a greater uptake into intestinal Peyer's patches. Given the excellent results in the in vivo studies, it can be concluded that calcium loaded bovine serum albumin microspheres could be an effective and promising approach for the oral therapy of calcium. Indeed, this approach can be an alternative to parenteral therapy in acute hypocalcaemia as well.