Mackie, Argyle's joint top-scorer this season with five goals, has missed his side's last two games due to flu but returned to training last week and is now ready to return.
Centre-half Reda Johnson is also set to be available following Benin's elimination from the African Cup of Nations.
His return could be timely as there are injury concerns over fellow defenders Kari Arnason (leg) and Chris Barker (calf).
David Stockdale will challenge Romain Larrieu for the goalkeeper's jersey.
Stockdale arrived on loan from Fulham prior to last weekend's postponed fixture against Barnsley.
Argyle are 23rd in the table and six points from safety going into Tuesday night's game.
DJ Campbell comes back into the reckoning for Derby ahead of their trip.
The striker was ineligible for the FA Cup fourth-round tie against Doncaster on Saturday under the terms of his loan from Leicester.
He is likely to go straight into the starting line-up, with Kris Commons, Steven Davies, Rob Hulse and Chris Porter all vying to partner him.
Russell Anderson's first start for the Rams could come at the expense of Jake Buxton, who needed a pain-killing injection in his ribs to get through the 1-0 cup win over Doncaster.
With fellow centre-half Shaun Barker also playing through the discomfort of a knee problem, Anderson is expected to step into the heart of the defence.
Sporting Life