An implantable manually-actuated drug delivery device, consisting of a refillable drug reservoir, flexible cannula, check valve, and suture tabs, was investigated as a new approach for delivering pharmaceuticals to treat chronic ocular diseases. Devices are fabricated by molding and bonding three structured layers of polydimethylsiloxane. A 30 gauge non-coring needle was used to refill the reservoir; this size maximized the number of repeated refills while minimizing damage to the reservoir. The check valve cracking pressure was 76 +/- 8.5 mmHg (mean +/- SE, n = 4); the valve sustained > 2000 mmHg of reverse pressure without leakage. Constant delivery at 1.57 +/- 0.2 microL/sec and 0.61 +/- 0.2 microL/sec (mean +/- SE, n = 4) under 500 mmHg and 250 mmHg of applied pressure, respectively, was obtained in benchtop experiments. The valve closing time constant was 10.2 s for 500 mmHg and 14.2 s for 250 mmHg. Assembled devices were successfully demonstrated in benchtop, ex vivo, and in vivo experiments.