About 65,000 people will lose Medicaid coverage under the plan and most will move to Medicare, which is fully funded by the federal government.
Medicaid is paid by state and federal dollars and provides health coverage for the needy, aged, blind, disabled and low-income children with families.
A few hours after he signed the bill, about 100 people rallied at the Capitol to say Barbour should let legislators reconsider the Medicaid bill and undo some of the changes.
Barbour said he won't do that. The new law takes effect July 1.