In a previous study we investigated the interaction of CCK-8 with either insulin, glucagon or somatostatin in control and streptozotocin (STZ)-induced diabetic rats. Our results showed marked reduction in amylase secretion in diabetic rats compared to control (Singh et al., 1999). The cellular mechanisms underlying reduced amylase output during diabetes is still unclear. This study measures CCK-8-evoked calcium (Ca2+) mobilisation, α-amylase and CCK-A receptor mRNA gene expressions in pancreatic acinar cells of age-matched control and STZ-induced adult male diabetic rats using established methods. After two months of STZ treatment, diabetic animals gained significantly (Students′t-test; P<0.05) less weight and elevated blood glucose levels. Weights of diabetic and control rats were 219.8±6.8 g, (n=20) and 373.6±6.7 g, (n=20), respectively. Similarly, blood glucose levels were 380±25.9 mg dl-1 (n=20) and 73.3±3.4 mg dl-1 (n=20) in diabetic and control rats. The pancreas of diabetic rats (1.01±0.05 g, n=20) weighed significantly less (P〈0.05) compared to controls (1.29±0.07 g, n=20). Basal [Ca2+]i in control and diabetic fura-2 loaded pancreatic acinar cells were 251.1±17.1 nM (n=25) and 151.9±8.5 nM (n=39). Stimulation of control acinar cells with 10-8 M CCK-8 resulted in a rapid increase (peak response) in [Ca2+]i followed by a decline to a plateau phase which remained above the basal level for over 10 min. In diabetic acinar cells the CCK-8-evoked peak and plateau responses were significantly (P〈0.05) reduced compared to normal acinar cells. Typically, the CCK-8-evoked peak [Ca2+]i response was 3297.8±349.5 nM (n=25), and 2052.9±146.6 nM, (n=39). After 10 min of CCK-8 application the plateau [Ca2+]i was 351.7±30.6 nM (n=11) and 235.2±11.6 nM, (n=23) in control and diabetic acinar cells, respectively. α-amylase mRNA levels were significantly (P〈0.05) reduced in diabetic pancreatic samples compared to controls which had a significantly lower (P〈0.05) crossing-over value (8.54±0.131, n=8 vs, 17.96±0.272, n=7) compared to diabetic animals. Conversely, the mRNA gene expression levels of the CCK-A receptor remained unchanged between the two groups. Crossing-over values were 20.92±0.0104 (n=8) and 21.52±0.181 (n=7) for control and diabetic animals, respectively. The results indicate that STZ-induced diabetic exocrine pancreatic insufficiency may be associated with a derangement in cellular Ca2+ transport and reduced transcription of α-amylase, but not the CCK-A receptor mRNA.