Type 2 diabetes mellitus (T2DM) is a major global health problem currently affecting more than 220 million people. T2DM is associated with a number of symptoms and long term complications including neuropathy, cardiomyopathy, nephropathy, retinopathy, delayed wound healing and constant infections. This study investigated the effect of T2DM on intracellular free calcium concentration [Ca2+]i in neutrophils and lymphocytes from T2DM patients compared to healthy age-matched controls. The study had the relevant ethical clearance from LREC in UK and UNEX in Spain. Both neutrophils and lymphocytes were isolated by density gradient centrifugation using Ficoll histopaque and loaded with fura 2-AM. [Ca2+]i was measured using established fluorescent method. Changes in [Ca2+]c were calculated using the fura-2 340/380 ratio. Mean (± SD) basal [Ca2+]i was 100±11 nM (n=6) and 75.0±10 nM, (n=6) in healthy age-matched control neutrophils and lymphocytes, respectively. In T2DM patients [Ca2+]i was 92±10 nM (n=6) and 87±10 nM (n=6) in neutrophils and lymphocytes, respectively. These results show no significant difference in basal [Ca2+]i comparing control with T2DM in either neutrophils or lymphocytes. Stimulation of human neutrophils with 10-8 M fMLP resulted in transient and marked increases in [Ca2+]i above basal level reaching maximum within 15-25 sec, followed by a rapid decline in both age-matched control and T2DM cells. Peak [Ca2+]i was significantly (Student’s t-test; p<0.05) decreased in neutrophils from T2DM patients compared to age-matched controls. Typically, [Ca2+]i was 2.3×104 nM (n=6) and 0.08×104 nM (n=6) for control and T2DM neutrophils, respectively. Similarly, stimulation of neutrophils with 10-6 M thapsigargin resulted in a gradual increase in [Ca2+]i reaching maximum within 4-5 min. There was a significant (p<0.05) decrease in [Ca2+]i in T2DM human neutrophils compared to age-matched controls. [Ca2+]i was 9.0×104 nM (n=6) and 2.0×104 nM (n=6), in control and T2DM neutrophils, respectively. Stimulation of fura-2 loaded lymphocytes with 10-6 M thapsigargin resulted in gradual increases in [Ca2+]i in both age-matched control and T2DM. However, [Ca2+]i was significantly (p<0.05) less in lymphocytes from T2DM compared to age-matched control. Typically, [Ca2+]i was 9.0×104 nM (n=6) and 2.0×104 nM (n=6) in control and T2DM lymphocytes, respectively. Together, the present results have demonstrated that [Ca2+] homeostasis seemed to be deranged in both neutrophils and lymphocytes of T2DM patients compared to age-matched controls suggesting a relationship between cellular calcium and frequent infections normally associated with T2DM patients.