The aim of this research is to primarily determine the effect of calcium on isolated rat liver mitochondria and to discover the possible effects of adenosine and adenosine monophosphate on calcium induced mitochondrial swelling. About 100 male albino rats weighing between 180-260g were recruited into the study. The male albino rats were from animal house of Faculty of Biological Sciences, University of Nigeria, Nsukka. The effects of calcium, adenosine and adenosine monophosphate on isolated normal male rat liver mitochondria were studied and also the effects of adenosine and adenosine monophosphate on calcium-induced mitochondria were also studied by use of standard biochemical techniques and read at 520nm in spectrophotometer. From the study, we could infer that calcium at lower concentration will induce swelling of the mitochondria and invariably rapid swelling at higher concentration of calcium. It was also inferred that the magnitude of the effect of concentration of adenosine or adenosine monophosphate was invariably related to calcium concentration, hence prevented swelling in the presence of high concentration of calcium.