The aim of this study is to elucidate the effects of different dosages of octreotide on portal pressure in cirrhotic patients and to investigate the mechanism of activated human hepatic stellate cells (HSCs) on octreotide. Thirty-one (31) hepatitis B-related cirrhotic patients were randomly assigned to receive treatment with a 50 (group A, n = 12) or a 25 mu g/h infusion of octreotide for 72 h (group B, n = 14); the control group C (n = 5) received conventional treatment. Dynamic portal pressure was directly measured via a portal vein catheter. To study the cellular mechanism of octreotide, the expression of SSTRs 1-5 in LX-2, an HSC line, was examined by immunostaining and RT-PCR. Intracellular Ca2+ in LX2 was measured by laser scanning confocal microscopy (LSCM). The protein and mRNA levels in all five subtypes of SSTRs were positively expressed in LX-2. Octreotide led to an immediate two-fold drop in intracellular Ca2+ (P < 0.01). Portal pressure, in both groups A and B, decreased significantly (mean, -20.6%) after octreotide infusion. Octreotide decreased portal pressure in cirrhotic patients by inhibiting HSC contractility by decreasing intracellular Ca2+ concentration via stimulation of all SSTRs on HSCs.