The Republican congressman previously formed a finance committee and was widely anticipated to run. But he waited until Wednesday morning to announce the bid on Twitter.
Donnelly is considered one of the most vulnerable Senate Democrats in 2018. Republicans have signaled they will spend considerable sums to retake the seat previously held by former Sen. Dick Lugar.
But already the GOP primary is looking like it could be brutal. Messer and fellow Republican Rep. Todd Rokita have traded insults for weeks.
Rokita has yet to formally announce his candidacy but has hired key campaign staffers for an expected Senate bid.