The purpose of this study was to propose that intrapleural urokinase (UK) instillation could reduce pleural thickening in the treatment of loculated tuberculous pleural effusion. Forty- three patients who were initially diagnosed as having loculated tuberculous pleural effusion were assigned at random to receive either the combined treatment of UK instillation including anti-tuberculosis agents (UK group, 21 patients) or strictly the unaccompanied anti-tuberculous agents (control group, 22 patients). The UK group received 100,000 IU of UK dissolved in 150 ml of normal saline daily, introduced into the pleural cavity via a pig-tail catheter. The control group was treated with anti-tuberculous agents, excepting diagnostic thoracentesis. After the cessation of treatment, residual pleural thickening (RPT) was compared between the two groups. Clinical characteristics and pleural fluid biochemistry were also evaluated. The RPT (4.59 +/- 5.93 mm) of the UK group was significantly lower than that (18.6 +/- 26.37 mm) of the control group (p < 0.05). The interval of symptoms observed prior to treatment of patients with RPT > or = 10 mm (6.0 +/- 3.4 wks) was detected to be significantly longer than in those with RPT < 10 mm (2.1 +/- 1.2 wks) in the control group (p < 0.05). However, there were no discernible differences were seen in the pleural fluid parameter in patients with RPT > or = 10 mm, as compared to patients with RPT < 10 mm in the UK group. These results indicate that the treatment of loculated tuberculous pleural effusion with UK instillation via percutaneous transthoracic catheter can cause a successful reduction in pleural thickening.