The cause of death was not released.
In 2002, she gave $100 million to an obscure but influential literary association based in Chicago. The gift highlighted a personal detail -- Lilly had written poetry since the mid-1930s, to little acclaim.
"Poetry has no greater friend than Ruth Lilly," said John Barr, president of the Poetry Foundation, which received the grant, in the obituary posted online Thursday by the Indianapolis Star.
Lilly was born Aug. 2, 1915, in Indianapolis and lived there her entire life. She was the first of two children of Josiah K. Lilly Jr., whose grandfather founded the pharmaceutical company in 1876. She shared her first name, Ruth, with her mother.
At 26, she married Guernsey Van Riper, the son of a local advertising executive. The marriage lasted 40 years, but she spent many of them hospitalized as she struggled with severe depression.
The couple, who had no children, divorced in 1981.
In her 70s, Lilly found relief from her symptoms when she began to take Prozac, the antidepressant developed by Eli Lilly & Co. that came on the market in 1988.
Prozac "made a world of difference," her physician, Jack Hall, told the Star in 2002. "Prozac changed her life."
A family statement released Thursday said that during her later years, Lilly's philanthropy widened her circle of contacts and interests, and her life "became much more interesting and rewarding."