The mission is planned to deliver laboratory gear and mice for bone-loss experiments, as well as food and spare parts to keep it operating after the US space shuttles are retired next year.
As the assembly of the $100bn space station nears completion, Nasa and its partners - Russia, Europe, Japan and Canada - are shifting focus to research programmes.
Two refrigerator-sized racks for fluid physics and materials science experiments are among the seven tonnes of new gear set to be installed during Discovery's nine-day stay at the station.
Mice on board
Eight mice, including four that were genetically enhanced with a double portion of a bone-building gene, will be left on the station as part of a study to find out why astronauts' bones break down in the gravity-free world of space.
The affliction is similar to osteoporosis, the bone-destroying disease, which affects millions of people on Earth, particularly post-menopausal women, and occurs because bone breakdown outpaces replenishment.
The planned flight comes as the Obama administration begins to weigh options for the US human space programme, including extending the life of the space station beyond September 30, 2015, when funding is projected to end.
Nasa spends about half of its $18bn annual budget on human space programmes, including about $2.5bn a year to run the station, which is nearing completion after more than a decade of construction 355km above Earth.
The station will be as big as a football field and weigh nearly 408,000kg.