JOHANNESBURG, February 7, 2014 (AFP) - The injury-plagued Molinari's round included four birdies, leaving him on 11 under par at the end of day two, tied in the lead with Scotland's Craig Lee.
Molinari's 68 on the Royal Johannesburg & Kensington West Course followed a 64 on the easier lay-out East Course on Thursday.
The field play both courses on the first two days, then switch to the East Course after the cut.
Molinari, who played in the 2010 Ryder Cup but had seen his world ranking slip to 220, last week recorded a top ten finish in Dubai and said his good form was continuing on the latest global leg of the European tour.
"It was another good round of golf and I hit the ball very well," said the Italian.
"Maybe not as well as yesterday, but I gave myself a lot of chances on the East Course, but all of the par fives are reachable, so you can make a good score."
Molinari, who turns 33 next week, added: "I'm very happy with pretty much everything. I am very happy with my position and my game right now."
Lee, who shot a 67 on the West Course to go with a 65 on the East on the first day, said he achieved his aim of not slipping back into the field but conceded he "didn't really capitalise on the back nine".
One shot further back were England's David Horsey and the home favourite George Coetzee.
Horsey posted an eight under par 63, which included six birdies in the first 14 holes.
Despite his home backing, Coetzee has never won on home soil on the European Tour.
The four are being closely chased by a strong field with seven players just two shots off the lead on nine under, including Scotland's Alastair Forsyth.
The eventual winner of the Joburg Open will take home 206,050 euros and one of three automatic qualifications for the British Open.
Leading scores on Friday in the second round of the $1.77m Joburg Open on the European Tour on the East and West Courses of the Royal Johannesburg and Kensington Golf Club (pars 71 and 72):
132 - Edoardo Molinari (ITA), Craig Lee (SCO)
133 - David Horsey (ENG), George Coetzee (RSA)
134 - Jin Jeong (KOR), Justin Walters (RSA), James Heath (ENG), Andrew Georgiou (RSA), Alastair Forsyth (SCO), Roope Kakko (FIN), Danny Willett (ENG)
135 - Edouard Dubois (FRA), Thomas Aiken (RSA), Gary Stal (FRA), Brandon Stone (RSA), Gregory Bourdy (FRA)
136 - Tyrone Ryan (RSA), Jorge Campillo (SPA), Tyrell Hatton (ENG), Christiaan Basson (RSA), Eduardo De La Riva (SPA, Hennie Otto (RSA), Seve Benson (ENG), James Morrison (ENG)