In this study, we have reported results of the investigation related to the influence of nickel ions on in vitro bio-activity of CaF2–CaO–B2O3–BaO–P2O5 glasses. The studies carried out are, degradation studies of the glass samples in SBF for a long time (for about a month), XRD, SEM and spectroscopic properties performed before and after immersion in simulated fluid suggested a thin coating of HAp crystalline grains on the surface of the glasses. IR and Raman spectral studies have further confirmed the formation of HAp layer. Magnitude of fraction of the samples that are degraded in the fluid is evaluated by weight loss and pH of remaining fluid. Degradation results along with characterization studies as a function of concentration of NiO indicated an increasing quantity of HAp deposited on the samples with the rise of NiO quantity up to 0.6 mol%. Spectroscopic investigations have further indicated the nickel ions occupied Oh and Td positions in the glass network. The studies have also suggested Oh occupancy of these ions is dominant in the glass doped with 0.6 mol% of nickel oxide while the fraction of tetrahedral nickel ions is minimal in this glass. The scrutiny of the degradation study results in combination with spectroscopy studies indicated that higher concentration of octahedral nickel ions are preferable for achieving higher quantity of crystalline HAp layer on the surface of the samples while the tetrahedral nickel ions are hindrance in promoting the growth of HAp layer.